Natural products remain the most prolific source of new antimicrobials, and the chemical diversity of natural compounds is still unmatched by combinatorial chemistry approaches (Newman and Cragg, 2012). While the latter has been successfully applied for lead optimization, it basically failed to deliver genuinely new pharmacophores, especially in the field of antimicrobials. This is mainly due to limitations in the structural variety of compounds represented in combinatorial libraries. Most of the antibiotics in clinical use today have been developed from compounds isolated from bacteria and fungi, with members of the actinobacteria being the dominant source (Peláez F, 2006). Actinobacteria-derived antibiotics that are important in medicine include aminoglycosides, anthracyclines, chloramphenicol, macrolides, tetracyclines, etc. Traditionally, most of these antimicrobials have been isolated from soil-derived actinomycetes of the genus Streptomyces. 
However, isolation strategies in recent years have been directed to unexploited environments like marine sources. Bioprospecting efforts focusing on the isolation and screening of actinobacteria from ocean habitats have added new biodiversity to the order Actinomycetales and revealed a range of novel natural products of potential pharmacological value (Mincer 2001). The existence of marine actinobacterial species that are physiologically and phylogenetically distinct from their terrestrial relatives is now widely accepted, and new taxonomic groups of marine actinomycetes have been described for at least six different families within the order Actinomycetales (Fenical et al 2006).
Apart from being phylogenetically distinct from their terrestrial relatives, marine isolates have been shown to possess specific physiological adaptations (e.g., to high salinity/osmolarity and pressure) to their maritime surroundings. The immense diversity of this habitat along with its underexploitation is the fundamental reason for attracting researchers toward it for discovering novel metabolite producers. There is an occurrence of distinct rare genera in the marine ecosystem, and many were found to produce novel and chemically diverse secondary metabolites (Riedlinger 2004), (Zotchev, 2012), (Manivasagan et al., 2014).
Most streptomycetes and other filamentous actinomycetes possess numerous gene clusters for the biosynthesis of secondary metabolites (Bentley et al 2002), and genome sequence studies have revealed that large portions of their genomes are devoted to secondary metabolite biosynthesis. Several gene clusters coding for known or predicted secondary metabolites has been identified in the genome of different Streptomyces strains (Brautaset et al 2003), and the marine actinomycete Salinispora (Bode et al, 2002). Many medicinally important natural products, including antibacterials and antifungals, are synthesized by these multimodular assembly lines, and genome mining for secondary metabolite gene clusters has become a common tool to assess the genetic capability of bacteria to produce novel bioactive compounds (Fischbach and Walsh, 2006).
However, even for well-studied model antibiotic producers like Streptomyces coelicolor A3(2), discrepancies between the number of known metabolites on the one hand and the number of pathways identified from genomic data on the other hand are tremendous (Bentley et al 2002). These discrepancies can only be explained by the facts that most gene clusters for secondary metabolites are silenced under standard laboratory cultivation conditions and that an expression or upregulation of these pathways is only triggered in response to certain environmental signals. It has been shown that by cultivating bacteria under a range of conditions, it is possible to obtain products of many of these “orphan” biosynthetic pathways (Bode, 2002).
In Engelhardt et al (2010), twenty-seven marine sediment- and sponge-derived actinomycetes were classified at the genus level using molecular taxonomy. As described, PCR-screenings for genes involved in polyketide and non-ribosomal peptide antibiotic synthesis was used for analyzing the actinomycetes potential to produce bioactive secondary metabolites.
Most of the antibiotics in clinical use today were discovered more than 5 decades ago. Over the last 10 years, only two new antibacterial agents with new mechanisms of action (the synthetic oxazolidinone linezolid and the natural-product-based lipopeptide daptomycin) have been approved. Loss of efficacy of existing drugs due to emerging multidrug resistant pathogens threatens to outpace the development of new antimicrobials. The majority of all anti-infective drugs are either derived from or inspired by natural products. Accordingly, new antibiotics are most likely to come from natural product-based research since neither genomics-derived target based research nor combinatorial chemistry has so far provided drugs that have actually entered the market.
Thus, mining microbial diversity represents the most promising source for obtaining new and diverse antimicrobial leads to meet the challenges with emerging multidrug-resistance.